This invention relates to a system and method for salvaging or recovering blood to reduce net blood loss during surgery or other medical procedure and selectively removing solutes from plasma. More particularly, the invention relates to a system and method for removing excess water and/or fluid from whole blood or plasma and selectively removing solutes, such as drugs (e.g. heparin), autoantibodies, toxins, antigens, plasma components, and lipids (e.g. cholesterol) from plasma such that the treated blood can be administered directly to the patient or saved for later administration.
A patient undergoing major cardiac surgery with cardiopulmonary bypass (CPB) can lose a significant amount of blood. If the blood loss is profuse, the patient may require the administration of homologous blood products. Homologous blood products can sometimes be in short supply and may carry blood-borne pathogens.
To reduce the amount of blood loss during surgery and thus the need for administration of homologous blood products, several methods of intraoperative blood salvage or autotransfusion have been tried. These methods include administration of drugs (e.g. aprotinin, .epsilon.-amino caproic acid), hemoconcentration, modified ultrafiltration, cell washing, autologous predonation of blood for perioperative reinfusion, and autotransfusion of processed shed blood. J. Boldt et al., Blood Conservation in Cardiac Operations--Cell Separation Versus Hemofiltration, 97 J. Thorac. Cardiovasc. Surg. 832 (1989); Y. Nakamura et al., Comparative Study of Cell Saver and Ultrafiltration Nontransfusion in Cardiac Surgery, 49 Ann. Thorac. Surg. 973 (1990); J. Boldt et al., Six Different Hemofiltration Devices for Blood Conservation in Cardiac Surgery, 51 Ann. Thorac. Surg. 747 (1991); D. Tixier et al., Blood Saving in Cardiac Surgery: Simple Approach and Tendencies, 6 Perfusion 265 (1991); Y. Iu et al., Maximizing Blood Conservation in Cardiac Surgery, Perfusion Life 14 (July 1994); R. Breyer et al., A Comparison of Cell Saver Versus Ultrafilter During Coronary Artery Bypass Operations, 90 J. Thorac. Cardiovasc. Surg. 736 (1985); P. Page, Ultrafiltration Versus Cell Washing for Blood Concentration, 22 J. Extra-Corp. Tech. 142 (1990); H. Johnson et al., Comparative Analysis of Recovery of Cardiopulmonary Bypass Residual Blood: Cell Saver vs. Hemoconcentrator, 26 J. Extra-Corp. Tech. 194 (1994); J. Morris & Y. Tan, Autotransfusion: Is There a Benefit in a Current Practice of Aggressive Blood Conservation?, 58 Ann. Thorac. Surg. 502 (1994). Of these techniques, hemoconcentration and cell washing are among the most commonly encountered.
Hemoconcentration or ultrafiltration extracts water and low molecular weight solutes from the plasma fraction of whole blood. Plasma proteins, including proteins involved in the coagulation cascade, remain relatively intact. Hemoconcentrators are generally small, compact, cost-effective, and can be added to an existing CPB circuit without major modifications. A disadvantage of hemoconcentration is that debris cannot be removed, thus shed blood collected during surgery cannot be processed through a hemoconcentrator unless it has first been filtered, i.e. through a cardiotomy reservoir. Moreover, hemoconcentration does not remove heparin from the blood, thus even though water has been removed, the blood remains fully heparinized. Another disadvantage is that plasma-free hemoglobin, which results from hemolysis and is known to be toxic to the kidneys, is not effectively removed by hemoconcentration filters.
Cell washing is a method of blood concentration wherein whole blood is subjected to centrifugation while being rinsed with a saline solution. Cell washing removes debris, plasma-free hemoglobin, and heparin, thus the method can be used on shed blood as well as blood remaining in the CPB circuit and cardiotomy reservoir. A major disadvantage of cell washing is that all of the plasma proteins, including coagulation proteins, are discarded. Platelets are lost as well. Further, cell washing requires that a separate system, including a centrifuge, be dedicated for such a procedure. Therefore, the process of cell washing is more expensive than hemoconcentration. Moreover, since coagulation proteins are removed in the process, it is sometimes necessary to administer replacement factors after cell washing.
Shettigar et al., U.S. Pat. No. 5,211,850, describes a plasma membrane sorbent system for removal of solutes from blood. The system comprises a bundle of U-shaped hollow fibers immersed in an electrolyte solution with a sorbent contained in a closed plasma chamber. As blood flows through the entry arm, plasma filtration into the plasma chamber occurs. Solutes in the plasma are selectively depleted in the plasma chamber through binding to the sorbents. The purified plasma then reenters the membrane by reverse filtration.
S. Ash et al., U.S. Pat. No. 4,071,444, discloses a portable "flat plate" reactor for use as an artificial kidney. The device comprises a sealed outer casing that is divided internally by a series of flexible membranes into chambers adapted to receive blood and other chambers adapted to receive a solution containing water, activated charcoal, zirconium phosphate, zirconium oxide and urease or other sorbents for absorbing the urea and creatinine drawn through the membrane from the blood.
S. Ash, U.S. Pat. No. 4,348,283, describes a dialyzer for use as an artificial kidney or extracorporeal mass transfer device. The device comprises a plurality of dialyzer units, each unit comprising a pair of semipermeable membranes spaced apart by a gasket such that a blood chamber is formed between the membranes. Spacers are used to separate the dialyzer units and support the membranes. The spaces between the dialyzer units form dialysis chambers, which contain a suspension of sorbents, such as activated charcoal, calcium-sodium loaded zeolites, and/or urease.
S. Ash, U.S. Pat. No. 4,581,141, teaches a dialysis material and method for removing uremic substances, wherein the dialysis material comprises an aqueous slurry containing charcoal, a highly calcium-loaded zeolite cation exchanger, a purified urease, a suspending agent such as methylcellulose, and an aliphatic carboxylic acid resin in the acid form.
S. Ash, U.S. Pat. No. 4,661,246, discloses a dialysis instrument with a pump on the dialysate side of the instrument for moving blood through the instrument. The instrument contains a sorbent column for purification of the dialysate, the sorbent column containing activated charcoal, immobilized urease, zirconium phosphate cation exchanger, and zirconium oxide anion exchanger.
S. Ash, U.S. Pat. No. 5,277,820, describes a device and method for extracorporeal treatment of blood for the removal of toxins. A sorbent suspension is used for removing such toxins wherein the sorbent comprises a powdered surface adsorptive agent such as activated charcoal, physiological electrolytes, a cation exchanger for removing ammonium ions and the like, and macromolecular flow inducing agents such as polyoxyalkylene derivatives of propylene glycol or polyvinylpyrrolidone. Cisplatin and methotrexate could be removed from the blood by this method.
These apparatuses and methods all lack the ability to be used for both hemoconcentration and removal of selected solutes from the blood.
In view of the foregoing, it will be appreciated that development of a system and process that removes excess water and/or fluid from whole blood or plasma, conserves plasma proteins including coagulation proteins, reduces and/or removes plasma-free hemoglobin and heparin and other targeted molecules, is cost effective, and is easily used and incorporated into an existing CPB circuit or in parallel with a CPB circuit, in contrast to the prior art where expensive, stand-alone devices are used and perhaps require additional personnel to operative them, would be a significant advancement in the art.